Physiologists have long recognized that the hypothalamus controls the secretory functions of the adenohypophysis with the hypothalamus producing special substances which stimulate or inhibit the secretion of each pituitary hormone. Hypothalamic releasing factors have been characterized for the pituitary hormone thyrotropin (the tripeptide TRF), for the pituitary gonadotropins luteinising hormone and follicle stimulating hormone (the decapeptide LRF, LH-RH or GnRH) and for the pituitary hormone and adreno-corticotropin (the 41-amino acid polypeptide CRF). An inhibitory factor, called somatostatin, has also been characterized in the form of a tetradecapeptide which inhibits the secretion of growth hormone (GH). GH releasing factors (GRFs) have been isolated from human pancreatic tumor as well as rat, porcine, borine, ovine, caprine and human hypothalami. With the exception of the rat, all characterized GRFs containing 44 amino acids with an amidated carboxy-terminus. Each of these hypophysiotropic factors has been reproduced by total synthesis. Analogs of the native structures have also been synthesized in order to elucidate structure-activity relationships and, eventually, to provide synthetic congoners with improved properties, such as increased hormonal activity and/or 10 metabolic stability Studies with the synthetic human growth hormone releasing factor (hGRF and its analogs (N. Ling., et al, Biochem. Biophys. Res. Commun., (1984), vol. 122, pp. 304-310; vol. 123, pp. 854-861; V. A. Lance, et al., Biochem. Biophys. Res. Commun., 1984, vol. 119, pp. 165-272)) have revealed that
(a) deletion of the NH.sub.2 -terminal tyrosine residue of hGRF causes its activity to drop to 0.1%; N-acetylation of this residue or change of replacement of L by D isomers lowers the in vitro bioactivity of hGRF (1-40)--OH to 2-3%, and causes a 10-12 fold increase in the in vivo potency of hGRF(1-29)--NH.sub.2 ; these findings indicate that the presence of said residue is essential for imparting the hGRF molecule with high bioactivity;
(b) fragments containing the first 29 residues at least, e.g., hGRF(1-29)--NH.sub.2 and hGRF(1-37)--NH.sub.2, have at least 50% of the potency of hGRF; further deletion of amino acids results in a marked decrease in bioactivity, 30 e.g., hGRF(1-27)--NH.sub.2 and hGRF(1-23)--NH.sub.2 exhibit 12% and 0.24% of the potency of hGRF, respectively; these findings indicate the significance of the arginine residue at position 29 of hGRF. It is also known that the 4-guanidino-butylamino group, the so-called agmatine (Agm) residue, can play the role of the arginine residue in certain peptides and has some influence in providing resistance to enzymatic degradation (S. Bajusz, et al., in: PEPTIDES, 1982, (K. Blaha and P. Melon, eds.), Walter Gruyter, Berlin-New York, 1983, pp. 643-647). Classical (solution) methods have only been employed for the preparation of agmatine peptides to date; it is desired to provide methodology for the solid-phase synthesis of these peptides using techniques of peptide synthesis which have proven to be suitable for preparing GRFs and their analogs.